SITUS INVERSUS, BRONCHIECTASIS AND SINUSITIS

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573

Report

of

a Family

with

Two

Cases

of

Kartagener’s

Triad

and

Two

Additional

Cases

of

Bronchiectasis

Among

Six

Siblings

By W. H. BERGSTROM, M.D., C. D. COOK,

M.D., J.

SCANNELL, M.D.,

AND WILLIAM BERENBERG, M.D. Boston

K

ARTAGENER’ in 1933 reported four cases of concurrent bronchiectasis, sinus

in-versus and sinusitis, a triad which now bears his name. Isolated instances of

the syndrome had previously been reported by Siewert2 and by Gunther.’ Up to the

pres-ent, 80 such cases have been recorded although in only 16 of these has clearcut

roentgeno-graphic evidence of bronchiectasis been presented. The 80 cases are summarized briefly

in table 1.

The coincidence of bronchiectasis and situs inversus-borne out by surveys’7 which

demonstrate that bronchiectasis occurs in 12 to 23% of cases of transposition of the

ER. 40

=

p

No Discuss

CHART 1. Diagram of R. Family.

viscera-supports the hypothesis advanced by Kartagener and others that hereditary

pre-disposition may be a determining factor in certain cases of bronchiectasis. This would

ap-pear to be true in the family that is the subject of the present report. Of this family of

From the Departments of Pediatrics and Surgery, Harvard Medical School, the Childrens Medical

Service and the Surgical Services of the Massachusetts General Hospital, and from the Children’s

Hos-pital, Childrens Medical Center, Boston.

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1 Siewertt

2 Oeri’4

3-4 Gunther3

1904 1 Infancy 21 M 1909 1

1923 2 ?

9-10 Nussel”

Siblings

? Mother (affected-lungs)

Neg.

?

Mother, ? nieces and

20-24 Adams and

Churchill6 25 Glaum’7 26-27 Cockayne’1 35-48 Olsen4 49 Richards 50 DelpU 51-52 Russakoff’#{176} Siblings Not given Neg. Neg. Not given

Siblings; 2 other siblings

had bronchiectasis

574 W. H. BERGSTROM, C. D. COOK,

J.

SCANNELL AND W. BERENBERG

The histories of the individual members of the family follow:

TABLE 1

COLLECTED CASES OF KARTAGENER’S SYNDROME

Author Year Cases Age at Age

Onset Seen Sex Family History

?

F

5-8 Kartagener’ 1933 4 6 mo. 14 F

Childhood 27 F

2Oyr. 32 F

Infancy 26 M

nephews

Neg.

Siblings

1934 2 Infancy 15 M

2yr. 14 F

11 Behrmann’6 1935 1 12 yr. 21 M

12-13 Kartagener’ 1935 2 5 yr. 32 F

?

Ff

14-19 Kartagener7 1935 6 59 yr. 58 F ?

Childhood 19 F

l2yr. 34 M ?

? 28 F ?

?

32 M

Infancy 26 F ?

1937 5 54yr. 9 F ?

20 yr. 22 M ?

Childhood 23 F

20 yr. 28 F(Negro) ?

Infancy 22 M ?

1938 1 1 yr. 17 F Neg.

1938 1 ? ? M Sister with situs inversus

totalis Neg. 27 Rosenthal’8 28 Nagy” 29 Cole’#{176} 30 Adland2’ 31-34 Lopez9

1939 1 8 yr. 28 M

1940 1 Infancy 8 F

1940 1 Infancy 22 M

1941 1 3yr. 11 F

1944 4? ? M

M

?

Fl

?

?J

1943 14 ? Survey

1944 1 3days ? M

1946 1 Childhood 22 M

1946 2? 34 M

?

7 F

53-80 Torgerson6 1947 28 ? Survey

81-82 Present Report 1949 2 17 mo. 6 M

2yr. 5 M

father and mother and six children, two siblings presented the picture of Kartagener’s

syndrome, two had bronchiectasis and sinusitis without dextrocardia and two were normal

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Father: HR., aged 41 yr., was in good health except for a chronic rhinitis and cough that had

persisted since an attack of acute frontal sinusitis at the age of 23 yr. He had been entirely well during

(hildhOod and free from respiratory disease. There was no history of chronic pulmonary or cardiac

disease among his relatives. Of 8 siblings, 4 were well, 2 had died in infancy and 2 at the age of 30,

of causes unknown.

Examination at the clinic at the request of the authors revealed no abnormal physical findings. Roentgen films and fluoroscopic examination of the chest and sinuses were within normal limits.

Mother: ER., aged 40 yr., had always been well. There was no family history of cardia or

respiratory disease. Four siblings and their children were living and well.

Eldest Son: HR.. aged 10 yr., was admitted to the Massachusetts General Hospital with a diagnosis

of bilateral bronchiectasis and sinusitis.

He presented a history of runny nose since infancy, frequent upper respiratory tract infections

FIG. 1. H. R., eldest boy. Right anterior oblique projection of bronchogram to show extensive

bronchiectasis involving entire left lower lobe and both segments of lingula. (Reproduced with the permission of W. B. Saunders Company.)

FIG. 2. W. R., fifth child. Reproduction of bronchograrn which demonstrates cylindrical

bronchi-etasis in left middle lobe.

and cough. At the age of 17 mo. he had had an attack of pneumonia and otitis media. From that time he had an almost constant purulent rhinitis and a chronic cough productive of yellowish sputum, punctuated by several attacks of bronchitis and pneumonia. He had not been short of breath or cyanotic. Physical development had been reasonably normal.

The profuse mucopurulent nasal discharge was obvious at the time of admission. Dullness at the

left base posteriorly and moist rales at both bases were noted. Roentgenographic examination of the

chest (see Fig. 1) showed collapse of the left lower lobe and the right middle lobe. Bronchography

demonstrated bronchiectasis in the corresponding areas. A bronchoscopy showed increased

muco-purulent bronchial secretions. A tuberculin test 1-1000 was negative. Vitamin A tolerance test was within normal limits.

Shortly after admission a large nasal polyp was removed and, after a preliminary course of aerosol

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J.

been disappointing in that he has continued to have a productive cough and in addition shows some

exertional dyspnea and asthenia. His left upper lobe is now extensively involved by a chronic

suppurative process.

Pathologic examination of the operative specimen showed a completely collapsed lobe that was

thick, edematous and “looked as if it had never been expanded.” The bronchi were prominent, dilated and extended almost to the pleural surfaces. The bronchial walls did not appear particularly atrophic;

their mucosa was irregularly wrinkled. The microscopic sections were reviewed by Dr. T. B. Mallory.

There was considerable variation from bronchus to bronchus in the preservation of epithelium,

musculature and cartilage. Islands of scar tissue enclosing epithelial-lined tubes and spaces were evi-dence of past infection as well as atelectasis; considerable obliterative endarteritis suggested both

infection and disuse. In short, the picture was in keeping with the ‘‘acquired’ ‘ type of bronchiectasis.

Final diagnosis : Chronic sinusitis, bilateral bronchiectasis, nasal polyposis.

Eldest Daughter: ER., aged 9 yr., was first admitted to the Children’s Medical Center at the age of 7 yr.

At 1 1 mo. of age and again at 6 yr., she had an acute middle ear infection. At the age of 4 yr., her

tonsils and adenoids had been removed. A second adenoidectomy had been performed at the age of

6#{188}yr. Since the age of 5#{189}yr. she had had a chronic productive cough and persistent purulent nasal discharge.

On admission at 9 yr. of age, the patient was thin but otherwise adequately developed. A profuse

mucopurulent nasal discharge was present and slight dullness, decreased breath sounds and rales were

noted at the base of the right lung. Bronchograms demonstrated bronchiectasis of the right middle

and right lower lobes, with partial atelectasis of the former. Sinus films showed considerable clouding of both antra and the ethmoid cells. A tuberculin test 1:10 was negative.

Several 6 wk. courses of aerosol penicillin and streptomycin were ineffective. Finally, 1 yr. after admission, a right middle lobectomy was performed, followed by marked clinical improvement of the

patient. Pathologic report confirmed the diagnosis of bronchiectasis with chronic pneurnonitis. No

gross definite sacculation of the bronchi was found, but the walls were not firm as normal and the

bronchi appeared abnormally large. There was considerable fibrosis in the peribronchial area and

the alveolar septa were thickened.

Bilateral nasal polypectomies were performed 14 mo. later for persistent nasal discharge and

mouth breathing. At the last follow-up examination 1#{189}yr. postlobectomy, she was essentially

asymptomatic.

Final Diagnosis: Rhinitis, nasal polyposis, sinusitis, bronchiectasis, right middle and right lower lobe.

Third Child: E.R., a 7 yr. old boy, was in apparent good health. On examination at the Children’s Clinic of the Massachusetts General Hospital, no abnormalities were detected.

Fourth Child: R.R., a 6 yr. old boy, was admitted to the Children’s Medical Center for evaluation

of cyanosis persistent since his birth. Since the age of 2 yr., he had had continual nasal obstruction with thick purulent discharge and frequent loose cough. His motor development had been retarded, but

mental development was normal. He attended school and played actively with only slight dyspnea.

He did not squat. He had no dysphagia, stridor or chest pain.

The patient’s cyanosis was moderately severe and his respiration slightly labored. Marked clubbing of the fingers and toes was present. No pulsations in the neck were noted. He had a thick, purulent nasal discharge on the right and coarse rhonchi and crepitant rales were heard at both lung bases.

The cardiac dullness extended to the right of the sternum and there was a palpable thrill in the

third interspace at the right sternal border associated with a harsh systolic murmur transmitted to

the base of the heart and the right clavicle. The second heart sound was loud and snapping. Blood

pressure in the right arm was 88/58 mm/Hg, in the left 82/50 mm/Hg. Pulsations in the feet

were normal.

Hemoglobin was 16.5 gm./100 cc. Circulation time with decholin was 4 and 19 sec.

Electro-cardiogram showed inversion of all complexes in leads 1and 2. Roentgenographic examination of the

chest showed dextrocardia, cardiac enlargement, particularly in the region of the left ventricle, and engorgement of the pulmonary vessels. The plain films were suggestive of bilateral bronchiectasis.

Angiocardiography demonstrated an enlarged aoFta arising on the right and descending on the left.

The stomach bubble was on the right, liver dullness on the left. Sinus films were consistent with

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No treatment was given and the patient’s condition 5 mo. after discharge remained unchanged.

Final Diagnosis: Chronic sinusitis, situs inversus totalis, congenital heart disease with cyanosis,

bilateral bronchiectasis.

Fifth Child: W.R., a 5 yr. old boy, was admitted to the Massachusetts General Hospital with a

diag-nosis of otitis media of 3 wk.’ duration. Since the age of 2 yr. the child had had an almost constant nasal discharge and loose cough. His symptoms were intensified by frequent colds. He had had no dyspnea or cyanosis.

A perforation of the left ear drum was noted on admission. Coarse breath sounds, scattered rhonchi

and bubbling rales were heard over both lung fields. Cardiac dullness lay to the right of the sternum and the apical impulse lay in the right fifth interspace. The heart was not enlarged and the sounds were normal. Liver dullness was percussed to the left and gastric tympany to the right. Mild hypo-spadias was present. Plain films of the chest, confirmed by bronchography, demonstrated bronchiectasis and collapse of the left middle lobe (see Fig. 2).

Cardiac shadow and aorta lay on the right. Sinus films revealed pansinusitis. ECG was consistent with dextrocardia, but otherwise normal.

Penicillin therapy resulted in clearing of the middle ear infection but had no apparent effect on the bronchiectasis. Aerosol therapy was technically impossible. Patient was discharged to the Children’s

Medical Out-Patient Department at his mother’s request, since at that time she had 3 other children

hospitalized and the child’s problem did not seem urgent.

Final Diagnosis: Bronchiectasis, left middle lobe, pansinusitis, situs inversus totalis.

Youngest Child: J. R., a 3 yr. old boy, had always been entirely well with no history of chronic respiratory tract disease. When examined in the Children’s Medical Out-Patient Clinic, Massachusetts General Hospital, no abnormalities were noted.

DISCUSSION

Four members of the family here reported had clinical bronchiectasis of the so-called

acquired type with symptoms that began in early childhood. In all four, profuse nasal

dis-charge was a prominent feature. Two of the four had complete transposition of the

viscera as well, and these two had additional anomalies : one, hypospadias

;

the other,

con-genital heart disease with cyanosis. No history of complicating infectious disease

during any pregnancy was obtained from the mother. Two siblings had bronchiectasis that

required lobectomy. Two siblings were healthy and the traceable family presented no

sig-nificant history of respiratory tract disease.

Among the previously reported cases of Kartagener’s triad, there are three families in

which more than one member was so afflicted. Gunther3 reported two sisters among four

siblings. A parent, five aunts and an uncle were all free of the disease. KartagenerTM

re-ported two sisters with the triad and a brother normal except for epilepsy. Lopez9 found

two brothers and a sister with situs inversus, bronchiectasis and sinusitis. The present

in-vestigators have found no previous report of the multiple occurrence in a single family of

Kartagener’s triad plus bronchiectasis in other members.

Torgersen6 reports a 25% incidence of bronchiectasis and nasal polyposis among 77

siblings of 28 persons with Kartagener’s syndrome, while among 496 siblings of 93

per-Sons with situs inversus alone, he found only three nasal polyps and none with

bronchiec-tasis. These findings are illuminating in view of the inference which can be drawn from

frequency statistics that certain persons with situs inversus may have a genetic

predisposi-tion to bronchiectasis. Situs inversus occurs in approximately one in 8000 persons.3’5’#{176}”#{176}

Bronchiectasis is found in from 12 to 23% of persons with situs inversus, but in only .3

to .5% of the general hospital and clinical population.’5 It is of interest that such a

genetic predisposition to bronchiectasis is not manifest in the siblings of persons with

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triad. This apparent genetic difference between situs inversus alone and situs

inversus-bronchiectasis-sinusitis would support the suggestion of Adams and Churchill5 that situs

inversus may result either from a mutation affecting the genetic composition of the

zygote, or from environmental influences acting prior to or during the earliest stages of

cell division. It is of interest to note Olsen’s report4 of 1 1 of 85 patients with situs inversus

who had additional anomalies, including congenital heart disease, hydrocephalus,

imper-forate anus, cleft palate, flail thumb and accessory digits. Cockayne” found among 55

un-selected cases of situs inversus five with congenital heart disease, and lists from the

litera-ture 40 cases of such association, including 15 with a diagnosis of tetralogy of Fallot. That

Kartagener’s syndrome is a pediatric problem is shown in table 2. Approximately 90%

of the cases in which details as to age at onset of symptoms were given began at 14 years

or under.

It seems not unlikely that the combination in a single family of two siblings with

Kar-tagener’s triad and two with bronchiectasis alone may be the result of the same unknown

TABLE 2

AGE INCIDENCE AT ONSET OF SYMPTOMS IN KARTAGENER’S SYNDROME

2yr. and under 13

2tol4yr 10

l4yr.andover 3

Age not reported 55

mechanism that is responsible for the familial instance of monstrosities. Indeed, Adams and Churchill have pointed out that it is logical to regard persons with Kartagener’s triad

as monsters in a technical sense. This concept gains support from the fact that four family

groups, including the one here reported, have shown multiple occurrences of Kartagener’s

syndrome, whereas in only two instances1 has there been any suggestion of bronchial

dis-ease in the parents or children of persons with the triad. The horizontal distribution

ob-served, therefore, suggests an environmental factor active at the start of embryonic life,

rather than a genetic factor which should, if present, become apparent in more than one

generation. However, the extent and number of family histories available do not justify

any conclusion on this point.

It does seem reasonable to conclude, however, that such cases of bronchiectasis are the

result of antenatal influences, whether this be genetic or environmental. Whether this

con-genital abnormality be an actual structural defect, a physiologic failure of the respiratory

epithelium, or a predisposition to infection, cannot be answered on the basis of the

evi-dence here presented. Churchill” has recently proposed that an altered secretory activity

of the bronchial mucous membrane may constitute the basic abnormality that predisposes to

the development of the bronchiectasis. Examination of the resected specimens in the

pa-tients reported here failed to disclose unusual pathologic features and the bacteriologic

studies revealed nothing of significance. The profuse nasal discharge present in the four

children had always a certain element of complicating infection, so that the presence or

absence of a primary disturbance of the secretory function of respiratory epithelium could

(7)

bronchi-ectasis may be a mechanical one, i.e., the position of the great vessels may interfere with normal bronchial drainage, remains conjectural. It should be pointed out, however, that stillborn or newborn infants with dextrocardia do not have pathologic changes suggestive

of bronchiectasis.’3 In the present series of cases, the segmental pattern of the disease was

not out of the ordinary.

SUMMARY

A family is reported in which there occurred two cases of Kartagener’s triad and two

of bronchiectasis without situs inversus among six siblings. Eighty cases of Kartagener’s

triad previously reported are tabulated. The relation of this syndrome to the question of the etiology of bronchiectasis is discussed.

ACKNOWLEDGM ENT

The authors wish to acknowledge the assistance and suggestions offered by Drs. Allan M. Butler and Charles A. Janeway and roentgenographic intrepretations provided by Dr.

E. B. D.

Neuhauser.

REFERENCES

1. Kartagener, M., Zur Pathogenese der Bronchiektasien. I. Mitteilung: Bronchiektasien bei Situs

viscerum inversus, Beitr. z. KIm. d. Tuberk. 83:489, 1933.

2. Siewert, A. K., Ueber einem Fall von Bronchiektasie bei einem Patienten mit Situs Inversus

Viscerum, Berlin kIm. Wchnschr. 41: 139, 1904.

3. Gunther, 1-1., Die Biologische Bedeutung der Inversionen, Biol. Zentralbl. 43: 175, 1923.

4. Olsen, A. M., Bronchiectasis and dextrocardia: Observations on aetiology of bronchiectasis, Am.

Rev. Tuberc. 47:435, 1943.

5. Adams, R., and Churchill, E. D., Situs inversus, sinusitis, bronchiectasis: Report of five cases, including frequency statistics, J. Thoracic Surg. 7:206, 1937.

6. Torgersen, J., Transposition of viscera, bronchiectasis and nasal polyps: Genetical analysis and contribution to problem of constitution, Acta radiol. 28: 17, 1947.

7. Kartagener, M., and Horlacher, A., Bronchiektasien bei Situs viscerum inversus, Schweiz.

med. Wchnschr. 16:782, 1935.

8. Kartagener, M., and Horlacher, A., Zur pathogenese der Bronchiektasien, Situs Viscerum

In-versus und Polyposis nasi in einem Falle familiarar Bronchiektasien, Beitr. z. KIm. d. Tuberk.

87:331, 1935.

9. Lopez, A., Familial total visceral inversion, Rev. elm. espa#{241}. 14:378, 1944; abstracted, Arch. Pediat. 62:288, 1945.

10. Russakoff, A. H., and Katz, H. W., Dextrocardia and bronchiectasis: Review of literature and

report of two cases, New England J. Med.

235:253,

1946.

11. Cockayne, E. A., Genetics of transposition of viscera, Quart. J. Med. 7:479, 1938.

12. Churchill, E. D., Segmental and lobar physiology and pathology of lung, J. Thoracic Surg. 18:279, 1949.

13. Farber, S., and Hertig, A., Personal communication to the authors.

14. Oeri, R., Zur Kasuitik des Situs Viscerum inversus totalis, Frankfort Ztschr. J. path., Wiesb.

3:393, 1909.

1 5. Nussel, K., and Helbach, H., Bronchiektasien bei Situs viscerum inversus totalis, Beitr. z. KIm. d. Tuberk. 84:424, 1934.

16. Behrmann, A., Uber die Symptomentrias Situs inversus, Bronchiektasien, und Polyposis nasi,

Beitr. z. Kim. d. Tuberk. 86:161, 1935.

17. Glaum, K., Bronchiektasien bei Situs viscerum irversus totalis, Beitr. z. Klin. d. Tuberk. 91:422,

1938.

18. Rosenthal, D. B., Bronchiectasis and visceral transposition with report of case, M.

J.

Australia

1:761, 1939.

19. Nagy, L., tYber kongenitale Bronchiektasen an Hand eines Falles von Situs viscerum inversus

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J.

20. Cole, D. B., and Nails, W. L., Situs inversus, sinusitis and bronchiectasis, J. Thoracic Surg.

9:689, 1940.

21. Adland, S. A., and Einstein, R. A. J., Kartagener’s triad: Situs inversus viscerum, bronchiectasis and paranasal sinusitis, Am. J. Dis. Child. 61:1034, 1941.

22. Richards, W. F., Situs inversus viscerum, absent frontal sinuses with ethmoid and maxillary in-fection, and bronchiectasis: Kartagener’s triad, Tubercle 25:27, 1944.

23. Delp, M. H., Kartagener’s triad: Situs inversus, absent frontal sinuses with maxillary, ethmoid and sphenoid infection, and bronchiectasis, J. Kansas M. Soc. 47:93, 1946.

SPANISH ABSTRACT

Situs Inversus, Bronquiectasia y Sinusitis;

Reporte de dos Casos con la Triada de Kartagener y Dos Casos Adicionales

de Bronquiectasia Ocurridos en una Familia de Seis Hermanos

Los autores reportan una familia en la cual ocurrieron dos casos con La triada de Kartagener y

dos casos de bronquiectasia sin “situs inversus.” Se revisan y tabulan ochenta casos de la triad.a de Kartagener previamente reportados. Los autores discuten Ia relacion de este sindrome con ci origen etiologico de las bronquiectasias.

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1950;6;573

Pediatrics

W. H. BERGSTROM, C. D. COOK, J. SCANNELL and WILLIAM BERENBERG

Six Siblings

Two Cases of Kartagener's Triad and Two Additional Cases of Bronchiectasis Among